Not Applicable
1. Field of the Invention
The current invention relates to selective cooling, or hypothermia, of an organ, such as the brain, by cooling the blood flowing into the organ. This cooling can protect the tissue from injury caused by anoxia or trauma.
2. Background Information
Organs of the human body, such as the brain, kidney, and heart, are maintained at a constant temperature of approximately 37xc2x0 C. Cooling of organs below 35xc2x0 C. is known to provide cellular protection from anoxic damage caused by a disruption of blood supply, or by trauma. Cooling can also reduce swelling associated with these injuries.
Hypothermia is currently utilized in medicine and is sometimes performed to protect the brain from injury. Cooling of the brain is generally accomplished through whole body cooling to create a condition of total body hypothermia in the range of 20xc2x0 to 30xc2x0 C. This cooling is accomplished by immersing the patient in ice, by using cooling blankets, or by cooling the blood flowing externally through a cardiopulmonary bypass machine. U.S. Pat. No. 3,425,419 to Dato and U.S. Pat. No. 5,486,208 to Ginsburg disclose catheters for cooling the blood to create total body hypothermia.
Total body hypothermia to provide organ protection has a number of drawbacks. First, it creates cardiovascular problems, such as cardiac arrhythmias, reduced cardiac output, and increased systemic vascular resistance. These side effects can result in organ damage. These side effects are believed to be caused reflexively in response to the reduction in core body temperature. Second, total body hypothermia is difficult to administer. Immersing a patient in ice water clearly has its associated problems. Placement on cardiopulmonary bypass requires surgical intervention and specialists to operate the machine, and it is associated with a number of complications including bleeding and volume overload. Third, the time required to reduce the body temperature and the organ temperature is prolonged. Minimizing the time between injury and the onset of cooling has been shown to produce better clinical outcomes.
Some physicians have immersed the patient""s head in ice to provide brain cooling. There are also cooling helmets, or head gear, to perform the same. This approach suffers from the problems of slow cool down and poor temperature control due to the temperature gradient that must be established externally to internally. It has also been shown that complications associated with total body cooling, such as arrhythmia and decreased cardiac output, can also be caused by cooling of the face and head only.
Selective organ hypothermia has been studied by Schwartz, et. al. Utilizing baboons, blood was circulated and cooled externally from the body via the femoral artery and returned to the body through the carotid artery. This study showed that the brain could be selectively cooled to temperatures of 20xc2x0 C. without reducing the temperature of the entire body. Subsequently, cardiovascular complications associated with total body hypothermia did not occur. However, external circulation of the blood for cooling has not yet been a widely accepted approach for the treatment of humans. The risks of infection, bleeding, and fluid imbalance are great. Also, at least two arterial vessels must be punctured and cannulated. Further, percutaneous cannulation of the carotid artery is very difficult and potentially fatal, due to the associated arterial wall trauma. Also, this method could not be used to cool organs such as the kidneys, where the renal arteries cannot be directly cannulated percutaneously.
Selective organ hypothermia has also been attempted by perfusing the organ with a cold solution, such as saline or perflourocarbons. This is commonly done to protect the heart during heart surgery and is referred to as cardioplegia. This procedure has a number of drawbacks, including limited time of administration due to excessive volume accumulation, cost and inconvenience of maintaining the perfusate, and lack of effectiveness due to temperature dilution from the blood. Temperature dilution by the blood is a particular problem in high blood flow organs such as the brain. For cardioplegia, the blood flow to the heart is minimized, and therefore this effect is minimized.
Intravascular, selective organ hypothermia, created by cooling the blood flowing into the organ, is the ideal method. First, because only the target organ is cooled, complications associated with total body hypothermia are avoided. Second, because the blood is cooled intravascularly, or in situ, problems associated with external circulation of blood are eliminated. Third, only a single puncture and arterial vessel cannulation is required, and it can be performed at an easily accessible artery such as the femoral, subclavian, or brachial. Fourth, cold perfusate solutions are not required, thus eliminating problems with excessive fluid accumulation. This also eliminates the time, cost, and handling issues associated with providing and maintaining cold perfusate solution. Fifth, rapid cooling can be achieved. Sixth, precise temperature control is possible.
Previous inventors have disclosed the circulation of cold water or saline solution through an uninsulated catheter in a major vessel of the body to produce total body hypothermia. This approach has not been successful at selective organ hypothermia, for reasons demonstrated below.
The important factor related to catheter development for selective organ hypothermia is the small size of the typical feeding artery, and the need to prevent a significant reduction in blood flow when the catheter is placed in the artery. A significant reduction in blood flow would result in ischemic organ damage. While the diameter of the major vessels of the body, such as the vena cava and aorta, are as large as 15 to 20 mm., the diameter of the feeding artery of an organ is typically only 4.0 to 8.0 mm. Thus, a catheter residing in one of these arteries cannot be much larger than 2.0 to 3.0 mm. in outside diameter. It is not practical to construct a selective organ hypothermia catheter of this small size using the circulation of cold water or saline solution. Using the brain as an example, this point will be illustrated.
The brain typically has a blood flow rate of approximately 500 to 750 cc/min. Two carotid arteries feed this blood supply to the brain. The internal carotid is a small diameter artery that branches off of the common carotid near the angle of the jaw. To cool the brain, it is important to place some of the cooling portion of the catheter into the internal carotid artery, so as to minimize cooling of the face via the external carotid, since face cooling can result in complications, as discussed above. It would be desirable to cool the blood in this artery down to 32xc2x0 C., to achieve the desired cooling of the brain. To cool the blood in this artery by a 5xc2x0 C. drop, from 37xc2x0 C. down to 32xc2x0 C., requires between 100 and 150 watts of refrigeration power.
In order to reach the internal carotid artery from a femoral insertion point, an overall catheter length of approximately 100 cm. would be required. To avoid undue blockage of the blood flow, the outside diameter of the catheter can not exceed approximately 2 mm. Assuming a coaxial construction, this limitation in diameter would dictate an internal supply tube of about 0.70 mm. diameter, with return flow being between the internal tube and the external tube.
A catheter based on the circulation of fluid operates on the principle of transferring heat from the blood to raise the temperature of the water. The fluid must warm up to absorb heat and produce cooling. Water flowing at the rate of 5.0 grams/sec, at an initial temperature of 0xc2x0 C. and warming up to 5xc2x0 C., can absorb 100 watts of heat. Thus, the outer surface of the heat transfer element could only be maintained at 5xc2x0 C., instead of 0xc2x0 C. This will require the heat transfer element to have a surface area of approximately 1225 mm2. If a catheter of approximately 2.0 mm. diameter is assumed, the length of the heat transfer element would have to be approximately 20 cm.
In actuality, if circulated through an uninsulated catheter, the water or saline solution would undoubtedly warm up before it reached the heat transfer element, and provision of 0xc2x0 C. water at the heat transfer element would be impossible. Circulating a cold liquid through an uninsulated catheter also would cause cooling along the catheter body and could result in non-specific or total body hypothermia. Furthermore, to achieve this heat transfer rate, 5 grams/sec of water flow are required. To circulate water through a 100 cm. long, 0.70 mm. diameter supply tube at this rate produces a pressure drop of more than 3000 psi. This pressure exceeds the safety levels of many flexible medical grade plastic catheters. Further, it is doubtful whether a water pump that can generate these pressures and flow rates can be placed in an operating room.
The selective organ cooling achieved by the present invention is accomplished by placing a coaxial cooling catheter into the feeding artery of the organ. Cold perfluorocarbon fluid is circulated through the catheter. In the catheter, a shaft or body section would carry the perfluorocarbon fluid to a distal flexible heat transfer element where cooling would occur. A preferred heat transfer element would be bellows shaped. Cooling of the catheter tip to temperatures above minus 2xc2x0 C. results in cooling of the blood flowing into the organ located distally of the catheter tip, and subsequent cooling of the target organ. For example, the catheter could be placed into the internal carotid artery, to cool the brain. The size and location of this artery places significant demands on the size and flexibility of the catheter. Specifically, the outside diameter of the catheter must be minimized, so that the catheter can fit into the artery without compromising blood flow. An appropriate catheter for this application would have a flexible body of 70 to 100 cm. in length and 2.0 to 3.0 mm. in outside diameter.
It is important for the catheter to be flexible in order to successfully navigate the arterial path, and this is especially true of the distal end of the catheter. So, the distal end of the catheter must have a flexible heat transfer element, which is composed of a material which conducts heat better than the remainder of the catheter. The catheter body material could be nylon or PBAX, and the heat transfer element could be made from a material having higher thermal conductivity, such as nitinol, nickel, copper, silver, or gold. Ideally, the heat transfer element is formed with a maximized or convoluted surface area, such as a bellows. A bellows has a convoluted surface, with fin-like annular folds, causing the bellows to be very flexible, even though the bellows is constructed of a metallic material. Further, the convoluted surface of the bellows causes it to have a much larger surface area than a straight tube of the same length. Still further, the bellows is axially compressible, making it ideal for use on the tip of a catheter which will be navigated through the vascular system of a patient. If the bellows abuts the wall of an artery, the bellows will easily compress, thereby eliminating or reducing the trauma to the arterial wall.
Bellows can be formed with known techniques to be seamless and non-porous, therefore being impermeable to gas. Metallic bellows in the sizes appropriate for use in the present invention are known, which have helium leak rates less than 10xe2x88x926 cc/sec. Impermeability and low leakage are particularly important for use in the present invention, where refrigerant gas will be circulated through the vascular system of a patient.
Bellows are also mechanically robust, being capable of withstanding more than 10,000 cycles of axial loading and unloading. Further, metallic bellows are known to tolerate the cryogenic temperatures generated in the device of the present invention, without loss of performance. Finally, metallic bellows can be made in large quantities, relatively inexpensively, making them ideal for use in disposable medical device.
Because the catheter body and heat transfer element of the present invention may dwell in the vascular system of the patient for extended periods, up to 48 hours in some cases, they might be susceptible to blood clot formation if no preventive measures are taken. This is particularly true of the bellows design, because some blood stasis may occur in the annular folds of the bellows, allowing clot forming agents to cling to the bellows surface and form a thrombus. Therefore, treatment of the catheter body and bellows surfaces to prevent clot formation is desirable. One such treatment is the binding of antithrombogenic agents, such as heparin, to the surface. Another such treatment is the bombardment of the surface with ions, such as nitrogen ions, to harden and smooth the surface, thereby preventing clot forming agents from clinging to the surface.
The heat transfer element would require sufficient surface area to absorb 100 to 150 watts of heat, in the carotid artery example. This could be accomplished with a bellows element of approximately 2 mm. diameter, 13 cm. in length, with a surface temperature of 0xc2x0 C. The cooling would be provided by the circulation of a perfluorocarbon fluid through an inner supply tube, returning through the annular space between the inner supply tube and the outer tubular catheter body. The inner tube has insulating means, such as longitudinal channels. The longitudinal channels can be filled with a gas, or evacuated. Further, the outer tube of the catheter body can have insulating means, such as longitudinal channels, which also can be filled with a gas or evacuated.
For example, a perfluorocarbon fluid flowing at a flow rate of between two (2) and three (3) grams/sec could provide between approximately 100 and 150 watts of refrigeration power. Utilizing an insulated catheter allows the cooling to be focused at the heat transfer element, thereby eliminating cooling along the catheter body. Utilizing perfluorocarbon fluid also lowers the fluid flow rate requirement, as compared to water or saline solution, to remove the necessary amount of heat from the blood. This is important because the required small diameter of the catheter would have higher pressure drops at higher flow rates.
The catheter would be built in a coaxial construction with a 1.25 mm. inner supply tube diameter and a 2.5 mm. outer return tube diameter. This results in tolerable pressure drops of the fluid along the catheter length, as well as minimizing the catheter size to facilitate carotid placement. The inner tube would carry the perfluorocarbon fluid to the heat transfer bellows element at the distal end of the catheter body. If a bellows surface temperature of 0xc2x0 C. is maintained, just above the freezing point of blood, then 940 mm2 of surface area in contact with the blood are required to lower the temperature of the blood by the specified 5xc2x0 C. drop. This translates to a 2.0 mm. diameter heat transfer bellows by 13 cm. in length. To generate 0xc2x0 C. on the bellows surface, the perfluorocarbon fluid must be supplied at a temperature of minus 50xc2x0 C.
It is important to use a perfluorocarbon fluid, for several reasons. First, these compounds have very low viscosities, even at low temperatures. Therefore, they can be circulated through small tubing at high flow rates, with much less pressure drop than water or saline solution. Second, they can be cooled below 0xc2x0 C. without freezing, allowing colder fluid to be delivered to the heat transfer element. Since more heat can be transferred to the lower temperature heat transfer element, lower flow rates are required to achieve the same cooling capacity as higher flow rates of water or saline. This further decreases the pressure drop experienced in the tubing. Since some warming is likely to occur along the catheter body, it is also helpful to use a fluid which can be cooled to a lower temperature, thereby delivering the desired cooling capacity at the distal tip of the catheter.
Third, perfluorocarbon fluids have very low surface tension, as compared to water or saline solution. This is important in applications where the heat transfer element has highly convoluted surface contours to maximize surface area, such as the bellows heat transfer element. A fluid with low surface tension will wet the internal surface of such a heat transfer element, resulting in increased heat transfer, whereas a fluid with a higher surface tension, such as water, which will not completely wet the surface. Fourth, perfluorocarbon fluids are inert and non-toxic compounds, even having been used as blood substitutes. This is an important safety concern, in the event of a leak. Finally, perfluorocarbon fluids are chemically compatible with many of the plastics which are used in making catheters. This is important, since catheter deterioration could be a serious problem in applications where the catheter may remain in the vascular system of the patient, circulating fluid, for long periods of time.
The novel features of this invention, as well as the invention itself, will be best understood from the attached drawings, taken along with the following description, in which similar reference characters refer to similar parts, and in which: